Instrumental Variables: Application and Limitations

Martens, Edwin P.; Pestman, Wiebe R.; de Boer, Anthonius; Belitser, Svetlana V.; Klungel, Olaf H.

doi:10.1097/01.ede.0000215160.88317.cb

Cited by 465Advanced Causal Inference TechniquesStatistical Methods in EpidemiologyMeta-analysis and systematic reviews

Instrumental Variables: Application and Limitations

Martens, Edwin P., Pestman, Wiebe R., de Boer, Anthonius, Belitser, Svetlana V., Klungel, Olaf H.·2006·Epidemiology

DOI 10.1097/01.ede.0000215160.88317.cb

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Abstract

To correct for confounding, the method of instrumental variables (IV) has been proposed. Its use in medical literature is still rather limited because of unfamiliarity or inapplicability. By introducing the method in a nontechnical way, we show that IV in a linear model is quite easy to understand and easy to apply once an appropriate instrumental variable has been identified. We also point out some limitations of the IV estimator when the instrumental variable is only weakly correlated with the exposure. The IV estimator will be imprecise (large standard error), biased when sample size is small, and biased in large samples when one of the assumptions is only slightly violated. For these reasons, it is advised to use an IV that is strongly correlated with exposure. However, we further show that under the assumptions required for the validity of the method, this correlation between IV and exposure is limited. Its maximum is low when confounding is strong, such as in case of confounding by indication. Finally, we show that in a study in which strong confounding is to be expected and an IV has been used that is moderately or strongly related to exposure, it is likely that the assumptions of IV are violated, resulting in a biased effect estimate. We conclude that instrumental variables can be useful in case of moderate confounding but are less useful when strong confounding exists, because strong instruments cannot be found and assumptions will be easily violated.

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IV analyses are an alternative estimation method that can be used to derive an estimate of the causal effect of the treatment on the outcome by accounting for the size of the association between randomization and the exposure.
“IV analyses are an alternative estimation method that can be used to derive an estimate of the causal effect of the treatment (here, CRP) on the outcome (SBP) by accounting for the size of the association between randomization and CRP.3,4,12–15”
From Mendelian randomization (2022) · cites this paper as [13]

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“However, it has been argued that the application of this method is limited because of its strong assumptions, making it difficult in practice to find a suitable instrumental variable.(16) The objectives of this article are first to introduce the application of the method of IV in epidemiology in a nontechnical way and…”
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Authors: Martens, E. P., Pestman, W. R., de Boer, A., Belitser, S. V., & Klungel, O. H.
Affiliations: Utrecht University (NL)
Corresponding author: Martens, Edwin P.
Belitser, Svetlana V.
Klungel, Olaf H.
ORCID: Belitser, Svetlana V.
Klungel, Olaf H.
Venue: Epidemiology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2006-05
Volume: 17
Issue: 3
Pages: 260-267
ISSN: 1044-3983 (ISSN-L)
DOI: 10.1097/01.ede.0000215160.88317.cb
OpenAlex: W2127065386
Cited by: 464
References: 37
Citations by year: 2026: 19 · 2025: 35 · 2024: 31 · 2023: 29 · 2022: 35 · 2021: 29 · 2020: 26 · 2019: 26 · 2018: 21 · 2017: 22 · 2016: 18 · 2015: 28 · 2014: 24 · 2013: 22 · 2012: 27
FWCI: 10.31
Type: journal article
Language: en
Open access: closed
Locations: Epidemiology (publishedVersion)
PubMed (publishedVersion)
Utrecht University Repository (Utrecht University) (submittedVersion)
Topics: Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Keywords: instrumental variables, confounding, confounding by indication, weak instruments, linear regression, exposure measurement error
MeSH terms: United States, Models, Statistical, Bias, Confounding Factors, Epidemiologic, Epidemiologic Studies

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Instrumental Variables: Application and Limitations

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